1. Bricault S, Dawson M, Lee J, Desai M, Schwalm M, Chung KS, DeTienne E, Fagan E, Li N, Becker A, Muthupalani S, Fränken JP, Pinotsis DA, Jasanoff A. Peripheral contributions to resting state brain dynamics. Nat Commun. 2024; 15(1): 10820.

The correlational structure of brain activity dynamics in the absence of stimuli or behavior is often taken to reveal intrinsic properties of neural function. To test the limits of this assumption, we analyzed peripheral contributions to resting state activity measured by fMRI in unanesthetized, chemically immobilized male rats that emulate human neuroimaging conditions. We find that perturbation of somatosensory input channels modifies correlation strengths that relate somatosensory areas both to one another and to higher-order brain regions, despite the absence of ostensible stimuli or movements. Resting state effects are mediated by the same peripheral and thalamic structures that relay responses to overt sensory stimuli. The impact of basal peripheral input is reduced in a rat model of autism, which displays both lower somatosensory functional connectivity and insensitivity to vibrissa inactivation. These results demonstrate the influence of extrinsic influences on resting state brain phenotypes in health and disease.

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2. Gong H, Lu Y, Deng SL, Lv KY, Luo J, Luo Y, Du ZL, Wu LF, Liu TY, Wang XQ, Zhao JH, Wang L, Xia ML, Zhu DM, Wang LW, Fan XT. Targeting S100A9 attenuates social dysfunction by modulating neuroinflammation and myelination in a mouse model of autism. Pharmacol Res. 2024: 107568.

Growing evidence supports a role for dysregulated neuroinflammation in autism. However, the underlying mechanisms of microglia-evoked neuroinflammation in the development of autistic phenotypes have not been elucidated. This study aimed to investigate the role and underlying mechanisms of microglial S100 calcium-binding protein A9 (S100A9) in autistic phenotypes. We utilized the BTBR T+ tf/J (BTBR) mouse, a reliable preclinical model for autism that displays core behavioral features of autism as well as persistent immune dysregulation. A combination of behavioral, pharmacological, immunological, genetic, molecular, and transcriptomics approaches were used to uncover the potential role of S100A9 in autism. Significant overexpression of microglial S100A9 was observed in the hippocampus of BTBR mice. BTBR mice displayed decreased social communication and increased repetitive behaviors compared to C57BL/6 mice. Interestingly, the above social dysfunction was attenuated by a pharmacological inhibitor of S100A9, accompanied by a significant reduction in the activated microglia morphological phenotype, inflammatory receptors, and proinflammatory cytokines. Notably, S100A9 inhibition decreased c-Fos(+) cells and promoted myelination in the cornu ammonis 3 of BTBR mice. Furthermore, the promyelinating compound administration ameliorated the autism-relevant behaviors in BTBR mice. Our findings indicate that microglia-derived S100A9 triggers the neuroinflammation cascade, myelination deficits, and social dysfunction. Targeting S100A9 could, therefore, be a promising therapeutic strategy for neuroinflammation-related neurodevelopmental disorders.

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3. Guillen-Parra M, Lin J, Prather AA, Wolkowitz OM, Picard M, Epel ES. The relationship between mitochondrial health, telomerase activity and longitudinal telomere attrition, considering the role of chronic stress. Sci Rep. 2024; 14(1): 31589.

Telomere attrition is a hallmark of biological aging, contributing to cellular replicative senescence. However, few studies have examined the determinants of telomere attrition in vivo in humans. Mitochondrial Health Index (MHI), a composite marker integrating mitochondrial energy-transformation capacity and content, may be one important mediator of telomere attrition, as it could impact telomerase activity, a direct regulator of telomere maintenance. In this observational longitudinal study, we examined in peripheral blood mononuclear cells (PBMCs), whether MHI predicted changes in telomerase activity over a 9-month period, thus impacting telomere maintenance over this same period of time. We secondarily examined the role of chronic stress, by comparing these relationships in mothers of children with an autism spectrum disorder (caregivers) vs. mothers of a neurotypical child (controls). Here we show that both chronic stress exposure and lower MHI independently predicted decreases in telomerase activity over the subsequent 9 months. Finally, changes in telomere length were directly related with changes in telomerase activity, and indirectly with MHI and chronic stress, as revealed by a path analysis. These results highlight the potential role of chronic stress and MHI as drivers of telomere attrition in human PBMCs, through an impairment of both energy-transformation capacity and telomerase production.

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4. Jacques-Fricke BT. Teaching Students to Effectively Evaluate Scientific Evidence and Advocate for Research in the Context of Autism Spectrum Disorder and the Neurodiversity Movement. Dev Biol. 2024.

Connecting socially relevant topics with biological content can boost student engagement and comprehension. Autism Spectrum Disorder (ASD) is an increasingly prevalent diagnosis with a number of intersecting topic areas between developmental biology and social justice. Here I describe two exercises that I developed to engage students in learning opportunities that link scientific process learning goals with real-world applications. First, students examine scientific research practices and work on connecting scientific evidence with conclusions by evaluating the retracted 1998 article by Andrew Wakefield that falsely linked the measles, mumps and rubella vaccination with the development of ASD. Second, students participate in a role-playing exercise to learn about the multiple viewpoints and perspectives that are involved in determining funding levels for scientific research in the United States, including learning about the neurodiversity movement and its impact on establishing ASD research priorities. By explicitly discussing appropriate scientific practices, analyzing the consequences of scientific misconduct and the spread of misinformation, and demonstrating how students can use their voices and their votes to support science funding, we can prepare students to become knowledgeable, empowered, scientifically literate citizens.

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5. Jin F, Wang Z. Mapping the structure of biomarkers in autism spectrum disorder: a review of the most influential studies. Front Neurosci. 2024; 18: 1514678.

BACKGROUND: Autism spectrum disorder is a distinctive developmental condition which is caused by an interaction between genetic vulnerability and environmental factors. Biomarkers play a crucial role in understanding disease characteristics for diagnosis, prognosis, and treatment. This study employs bibliometric analysis to identify and review the 100 top-cited articles’ characteristics, current research hotspots and future directions of autism biomarkers. METHODS: A comprehensive search of autism biomarkers studies was retrieved from the Web of Science Core Collection database with a combined keyword search strategy. A comprehensive analysis of the top 100 articles was conducted with CiteSpace, VOSviewer, and Excel, including citations, countries, authors, and keywords. RESULTS: The top 100 cited studies were published between 1988 and 2021, with the United States led in productivity. Core biomarkers such as genetics, children, oxidative stress, and mitochondrial dysfunction are well-established. Potential trends for future research may include brain studies, metabolomics, and associations with other psychiatric disorders. CONCLUSION: This pioneering bibliometric analysis provides a comprehensive compilation of the 100 most-cited studies on autism, which not only offers a valuable resource for doctors, and researchers but shedding insights into current shortcomings and future endeavors. Future research should prioritize the application of emerging technologies for biomarkers, longitudinal study of biomarkers, and specificity of autism biomarkers to advance the precision of ASD diagnosis and treatment.

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6. Liu H, Zhu X, Ge B, Huang M, Li X. The association between screen exposure and autism spectrum disorder in children: meta-analysis. Rev Environ Health. 2024.

INTRODUCTION: The goal is to provide light on the contentious relationship between screen exposure and childhood autism spectrum disorder (ASD). By conducting two meta-analyses that showed a potential association, including screen exposure effect by ASD and ASD risk by screen exposure, we aimed to clarify the potential causality between screen exposure and childhood ASD. CONTENT: The literature published up to December 2023 were systematically collected, and the combined effect values of weighted mean difference (WMD) and 95 % confidence interval (CI) and odds ratio (OR) and 95 % CI were calculated using two meta-analyses using the STATA 12.0. A total of 197,357 children, including 4,599 childhood ASD, were finally included in 10 studies. The results showed that children with ASD had higher levels of screen time exposure than healthy controls (combined effect value WMD=0.27, 95 % CI: 0.12-0.41, p<0.001). An increased risk of ASD was also found in children with high screen exposure compared to the low screen exposure group (OR=1.5395 % CI: 1.14-2.06). SUMMARY AND OUTLOOK: The development of childhood ASD may be associated with screen exposure. Future prospective studies are needed to verify the relationship between screen exposure and ASD in children.

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7. Lombardi E, Lepore F, Greer C. Improving Emergency Medical Services (EMS) Care for People With Autism in the Prehospital Setting Through Sensory and Communication Aids. Cureus. 2024; 16(11): e74702.

Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder characterized by social, communication, and behavioral challenges. Emergency medical services (EMS) environments, with their loud noises, bright lights, and unfamiliar personnel, often exacerbate these challenges, making care for individuals with ASD particularly complex. To address these challenges, the Franciscan Crown Point EMS system introduced the « Ben’s Blue Bags » (BBBs) program. These bags, available on every transport vehicle, contain sensory aids, headphones, a dry erase board for communication with nonverbal patients, and a pictogram of the human body for identifying injuries. The BBB program serves 18 different municipalities across four counties in Northwest Indiana, covering over 200 paramedics, 500 emergency medical technicians (EMTs), and 60 transport vehicles in both rural and urban settings. Over an eight-month period in 2023, 77 EMS providers participated in a survey assessing the effectiveness of BBBs. The results indicate that 94.2% of respondents found BBBs enhanced their ability to deliver high-quality care to individuals with ASD. Sensory aids were deemed the most valuable component, helping calm patients and reduce anxiety during EMS interventions. On a scale from 1 to 10, the mean rating was 9.08, with a standard deviation of 1.757, signifying that BBBs were « overwhelmingly helpful. » All but three respondents reported that BBBs were helpful in keeping individuals with ASD calm during interactions, and 58 out of 65 paramedics found BBBs useful for calming and/or distracting patients to enable intravenous (IV) placement. Additionally, 61 respondents reported at least one instance where an unnecessary emergency room visit was avoided due to help from BBBs. This study concludes that sensory aids and communication tools can significantly improve prehospital care for patients with ASD. We recommend the broader implementation of such tools and further research to explore their impact within EMS and emergency medicine.

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8. Mamun AA, Geng P, Wang S, Shao C, Xiao J. IUPHAR Review: Targeted Therapies of Signaling Pathways Based on the Gut Microbiome in Autism Spectrum Disorders: Mechanistic and Therapeutic Applications. Pharmacol Res. 2024: 107559.

Autism spectrum disorders (ASD) are complex neurodevelopmental disorders characterized by impairments in social interaction, communication and repetitive activities. Gut microbiota significantly influences behavior and neurodevelopment by regulating the gut-brain axis. This review explores gut microbiota-influenced treatments for ASD, focusing on their therapeutic applications and mechanistic insights. In addition, this review discusses the interactions between gut microbiota and the immune, metabolic and neuroendocrine systems, focusing on crucial microbial metabolites including short-chain fatty acids (SCFAs) and several neurotransmitters. Furthermore, the review explores various therapy methods including fecal microbiota transplantation, dietary modifications, probiotics and prebiotics and evaluates their safety and efficacy in reducing ASD symptoms. The discussion shows the potential of customized microbiome-based therapeutics and the integration of multi-omics methods to understand the underlying mechanisms. Moreover, the review explores the intricate relationship between gut microbiota and ASD, aiming to develop innovative therapies that utilize the gut microbiome to improve the clinical outcomes of ASD patients. Microbial metabolites such as neurotransmitter precursors, tryptophan metabolites and SCFAs affect brain development and behavior. Symptoms of ASD are linked to changes in these metabolites. Dysbiosis in the gut microbiome may impact neuroinflammatory processes linked to autism, negatively affecting immune signaling pathways. Research indicates that probiotics and prebiotics can improve gut microbiota and alleviate symptoms in ASD patients. Fecal microbiota transplantation may also improve behavioral symptoms and restore gut microbiota balance. The review emphasizes the need for further research on gut microbiota modification as a potential therapeutic approach for ASD, highlighting its potential in clinical settings.

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9. Mascari M, Cohen N, Yao M, Huang J, Lane J, Reeves KW, Balasubramanian R, Liu Z, Laouali N, Daniel LM, Chen CY, Seng CY, Shiao-Yng C, Kee MZL, Valvi D, Oulhote Y. Associations of Cord Blood Concentrations of Perfluoroalkyl Substances with Autistic Traits in Singaporean Children: The Growing Up in Singapore Towards Healthy Outcomes Study. Chemosphere. 2024: 144040.

BACKGROUND: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by social deficits and repetitive behaviors. Environmental pollutants may contribute to the etiology of ASD, but studies of perfluoroalkyl substances (PFAS) have shown conflicting results. OBJECTIVES: We assessed associations between cord blood concentrations of PFAS with autistic traits at age seven years in a Singaporean birth cohort. METHODS: We measured cord blood concentrations of eight PFAS in a sample of 430 mother-child pairs from the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) cohort. We assessed autistic traits using the Social Responsiveness Scale Second Edition (SRS-2) and its sub-scores, in which higher scores indicate more autistic traits. We estimated covariate-adjusted associations between the PFAS and SRS-2 scores using Bayesian weighted quantile sum (BWQS) regression models for the PFAS mixtures and multivariable regressions for single PFAS. We additionally evaluated effect modification by biological sex. RESULTS: We observed a positive association between the PFAS mixture and SRS-2 cognition sub-scores (β per SD increase=1.25 points, 95% CI -0.03, 2.40). Perfluorononanoic acid (PFNA) was the strongest contributor to the mixture effect. In single PFAS models, exposure to PFNA was associated with a higher SRS-2 total score (β=0.93 points, 95% CI 0.29, 1.58), cognition sub-score (β=1.26 points, 95% CI 0.55, 1.97), communication sub-score (β=0.88 points, 95% CI 0.20, 1.56), and restrictive and repetitive behaviors sub-score (β=0.93 points, 95% CI 0.23, 1.63). We also observed evidence of effect modification by sex for perfluoroundecanoic acid (PFUnDA) for the total score (p-effect modification [EM]=0.03), cognition sub-score (p-EM=0.03), and communication sub-score (p-EM=0.04), with negative associations seen in females and null associations in males. DISCUSSION: Cord blood PFAS concentrations were positively associated with autistic traits measured by SRS-2.

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10. Velladath SU, Kulkarni MM, Rege S, Edavana Santhosh S, Tiwari S, John S, Nayak R, Aroor S, Biju S, Ali Mohammed C. Evaluation of an interprofessional collaborative practice training module for the management of children with autism spectrum disorder. Med J Armed Forces India. 2024; 80(Suppl 1): S38-s42.

BACKGROUND: Protocols instituted for behavioral treatment and skills training programs for the management of autism spectrum disorder (ASD) suffer from lack of collaborative approaches. The tenets of interprofessional collaborative practice (IPCP) focus on preparing a panel of health care professionals (HCPs) from different professions who can work together to enable the common goal of ensuring that children with ASD can participate in society. This study was designed to pilot this approach through an IPCP training module on ASD for care providers from multiple professions. METHODS: An interventional study with pre-post analysis began with formation of the interprofessional (IP) team, who developed an IPCP module, addressing the knowledge and skills needed for the collaborative management of neurodevelopmental issues of children with ASD. This module was delivered through an online training workshop using various teaching learning methods to the participants from seven different health professions after obtaining informed consent. Perceptions of interprofessional collaboration and competencies of IPCP were assessed using standard IP tools and reflective summaries and analyzed through a mixed-methods approach. RESULTS: A total of 42 HCPs from seven professions, including speech and hearing, occupational therapy, clinical psychology, physiotherapy, pediatrics, nursing, and pedodontics, participated in the study. Pre-post analysis of PINCOM-Q and Dow-IPEC data and thematic analysis revealed a significant difference in the perceptions of interprofessional collaboration and competencies’ levels of IPCP. CONCLUSION: This study suggests that use of IPCP principles in the training of professionals working with ASD is a promising and feasible option to develop more competent health professionals. The training enhanced the abilities of professionals to work in field of ASD as conveyed by the participants. They also expressed confidence in the knowledge of IP core competencies after the completion of the module.

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11. Wu Q, Oh S, Tadayonnejad R, Feusner JD, Cockburn J, O’Doherty JP, Charpentier CJ. Individual differences in autism-like traits are associated with reduced goal emulation in a computational model of observational learning. Nat Ment Health. 2024; 2(9): 1032-44.

One’s ability to infer the goals and intentions of others is crucial for social interactions, and such social capabilities are broadly distributed across individuals. Autism-like traits (i.e., traits associated with autism spectrum disorder (ASD)) have been associated with reduced social inference, yet the underlying computational principles and social cognitive processes are not well characterized. Here we tackle this problem by investigating inference during social learning through computational modeling in two large cross-sectional samples of adult participants from the general population (N(1)=943, N(2)=352). Autism-like traits were extracted and isolated from other associated symptom dimensions through a factor analysis of the Social Responsiveness Scale. Participants completed an observational learning task that allowed quantifying the tradeoff between two social learning strategies: imitation (repeat the observed partner’s most recent action) and emulation (infer the observed partner’s goal). Autism-like traits were associated with reduced observational learning specifically through reduced emulation (but not imitation), revealing difficulties in social goal inference. This association held even when controlling for other model parameters (e.g., decision noise, heuristics), and was specifically related to social difficulties in autism but not social anxiety. The findings, replicated in an additional sample, provide a powerfully specific mechanistic hypothesis for social learning challenges in ASD, employing a computational psychiatry approach that could be applied to other disorders.

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12. Zhang Y, Lin L, Zhou D, Song Y, Stein A, Zhou S, Xu H, Zhao W, Cong F, Sun J, Li H, Du F. Age-related unstable transient states and imbalanced activation proportion of brain networks in people with autism spectrum disorder: A resting-state fMRI study using coactivation pattern analyses. Netw Neurosci. 2024; 8(4): 1173-91.

The atypical static brain functions related to the executive control network (ECN), default mode network (DMN), and salience network (SN) in people with autism spectrum disorder (ASD) has been widely reported. However, their transient functions in ASD are not clear. We aim to identify transient network states (TNSs) using coactivation pattern (CAP) analysis to characterize the age-related atypical transient functions in ASD. CAP analysis was performed on a resting-state fMRI dataset (78 ASD and 78 healthy control (CON) juveniles, 54 ASD and 54 CON adults). Six TNSs were divided into the DMN-TNSs, ECN-TNSs, and SN-TNSs. The DMN-TNSs were major states with the highest stability and proportion, and the ECN-TNSs and SN-TNSs were minor states. Age-related abnormalities on spatial stability and TNS proportion were found in ASD. The spatial stability of DMN-TNSs was found increasing with age in CON, but was not found in ASD. A lower proportion of DMN-TNSs was found in ASD compared with CON of the same age, and ASD juveniles had a higher proportion of SN-TNSs while ASD adults had a higher proportion of ECN-TNSs. The abnormalities on spatial stability and TNS proportion were related to social deficits. Our results provided new evidence for atypical transient brain functions in people with ASD. This article reveals the age-related atypical transient brain functions in autistic people. The default mode network dominates major states during rest, while the executive control network and salience network dominates minor states. Major states have more a stable coactivation patterns and higher proportion than minor states. The spatial stability would increase with age in healthy controls but not in autistic people. Meanwhile, autistic people spend less time on major states but more time on minor states. In addition, the unstable transient states and imbalanced activation proportion of brain networks are correlated with the social deficits. Although this work is limited by that single scanning data of only involving male participants with normal intelligence, it provides new transient aspect for atypical brain function in autistic people. eng.

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